Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Introduction

The WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical for achieving WHO End-TB targets. The Early Risk Assessment in TB Contacts by new diagno Stic t Ests (ERASE-TB) study aims to evaluate novel diagnostics and testing algorithms for early TB diagnosis and accurate prediction of disease progression among household contacts (HHCs) exposed to confirmed index cases in Mozambique, Tanzania and Zimbabwe.

Methods and analysis

A total of 2100 HHCs (aged ≥10 years) of adults with microbiologically-confirmed pulmonary TB will be recruited and followed up at 6-month intervals for 18–24 months. At each time point, a WHO symptom screen and digital chest radiograph (dCXR) will be performed, and blood and urine samples will be collected. Individuals screening positive (WHO symptom screen or dCXR) will be requested to provide sputum for Xpert MTB/Rif Ultra. At baseline, HHCs will also be screened for HIV, diabetes (HbA1c), chronic lung disease (spirometry), hypertension and anaemia. Study outcomes will be coprevalent TB (diagnosed at enrolment), incident TB (diagnosed during follow-up) or no TB at completion of follow-up. Novel diagnostics will be validated using fresh and biobanked samples with a nested case–control design. Cases are defined as HHCs diagnosed with TB (for early diagnosis) or with incident TB (for prediction of progression) and will be matched by age, sex and country to HHCs who remain healthy (controls). Statistical analyses will include assessment of diagnostic accuracy by constructing receiver operating curves and calculation of sensitivity and specificity.

Ethics and dissemination

ERASE-TB has been approved by regulatory and ethical committees in each African country and by each partner organisation. Consent, with additional assent for participants <18 years, is voluntary. Attestation by impartial witnesses is sought in case of illiteracy. Confidentiality of participants is being maintained throughout. Study findings will be presented at scientific conferences and published in peer-reviewed international journals.

Trial registration number

NCT04781257.Cite Now

Related collections

Most cited references 27

Record: found
Abstract: found
Article: found

Is Open Access

Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement

Gary S. Collins, Johannes Reitsma, Douglas G. Altman … (2015)

Prediction models are developed to aid health care providers in estimating the probability or risk that a specific disease or condition is present (diagnostic models) or that a specific event will occur in the future (prognostic models), to inform their decision making. However, the overwhelming evidence shows that the quality of reporting of prediction model studies is poor. Only with full and clear reporting of information on all aspects of a prediction model can risk of bias and potential usefulness of prediction models be adequately assessed. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) Initiative developed a set of recommendations for the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. This article describes how the TRIPOD Statement was developed. An extensive list of items based on a review of the literature was created, which was reduced after a Web-based survey and revised during a 3-day meeting in June 2011 with methodologists, health care professionals, and journal editors. The list was refined during several meetings of the steering group and in e-mail discussions with the wider group of TRIPOD contributors. The resulting TRIPOD Statement is a checklist of 22 items, deemed essential for transparent reporting of a prediction model study. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. The TRIPOD Statement is best used in conjunction with the TRIPOD explanation and elaboration document. To aid the editorial process and readers of prediction model studies, it is recommended that authors include a completed checklist in their submission (also available at www.tripod-statement.org). Editors’ note: In order to encourage dissemination of the TRIPOD Statement, this article is freely accessible on the Annals of Internal Medicine Web site (www.annals.org) and will be also published in BJOG, British Journal of Cancer, British Journal of Surgery, BMC Medicine, British Medical Journal, Circulation, Diabetic Medicine, European Journal of Clinical Investigation, European Urology, and Journal of Clinical Epidemiology. The authors jointly hold the copyright of this article. An accompanying Explanation and Elaboration article is freely available only on www.annals.org; Annals of Internal Medicine holds copyright for that article.

0 comments Cited 430 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice

Robert Trevethan (2017)

Within the context of screening tests, it is important to avoid misconceptions about sensitivity, specificity, and predictive values. In this article, therefore, foundations are first established concerning these metrics along with the first of several aspects of pliability that should be recognized in relation to those metrics. Clarification is then provided about the definitions of sensitivity, specificity, and predictive values and why researchers and clinicians can misunderstand and misrepresent them. Arguments are made that sensitivity and specificity should usually be applied only in the context of describing a screening test’s attributes relative to a reference standard; that predictive values are more appropriate and informative in actual screening contexts, but that sensitivity and specificity can be used for screening decisions about individual people if they are extremely high; that predictive values need not always be high and might be used to advantage by adjusting the sensitivity and specificity of screening tests; that, in screening contexts, researchers should provide information about all four metrics and how they were derived; and that, where necessary, consumers of health research should have the skills to interpret those metrics effectively for maximum benefit to clients and the healthcare system.

0 comments Cited 397 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study

Susan Dorman, Samuel G. Schumacher, David Alland … (2018)

Summary Background The Xpert MTB/RIF assay is an automated molecular test that has improved the detection of tuberculosis and rifampicin resistance, but its sensitivity is inadequate in patients with paucibacillary disease or HIV. Xpert MTB/RIF Ultra (Xpert Ultra) was developed to overcome this limitation. We compared the diagnostic performance of Xpert Ultra with that of Xpert for detection of tuberculosis and rifampicin resistance. Methods In this prospective, multicentre, diagnostic accuracy study, we recruited adults with pulmonary tuberculosis symptoms presenting at primary health-care centres and hospitals in eight countries (South Africa, Uganda, Kenya, India, China, Georgia, Belarus, and Brazil). Participants were allocated to the case detection group if no drugs had been taken for tuberculosis in the past 6 months or to the multidrug-resistance risk group if drugs for tuberculosis had been taken in the past 6 months, but drug resistance was suspected. Demographic information, medical history, chest imaging results, and HIV test results were recorded at enrolment, and each participant gave at least three sputum specimen on 2 separate days. Xpert and Xpert Ultra diagnostic performance in the same sputum specimen was compared with culture tests and drug susceptibility testing as reference standards. The primary objectives were to estimate and compare the sensitivity of Xpert Ultra test with that of Xpert for detection of smear-negative tuberculosis and rifampicin resistance and to estimate and compare Xpert Ultra and Xpert specificities for detection of rifampicin resistance. Study participants in the case detection group were included in all analyses, whereas participants in the multidrug-resistance risk group were only included in analyses of rifampicin-resistance detection. Findings Between Feb 18, and Dec 24, 2016, we enrolled 2368 participants for sputum sampling. 248 participants were excluded from the analysis, and 1753 participants were distributed to the case detection group (n=1439) and the multidrug-resistance risk group (n=314). Sensitivities of Xpert Ultra and Xpert were 63% and 46%, respectively, for the 137 participants with smear-negative and culture-positive sputum (difference of 17%, 95% CI 10 to 24); 90% and 77%, respectively, for the 115 HIV-positive participants with culture-positive sputum (13%, 6·4 to 21); and 88% and 83%, respectively, across all 462 participants with culture-positive sputum (5·4%, 3·3 to 8·0). Specificities of Xpert Ultra and Xpert for case detection were 96% and 98% (−2·7%, −3·9 to −1·7) overall, and 93% and 98% for patients with a history of tuberculosis. Xpert Ultra and Xpert performed similarly in detecting rifampicin resistance. Interpretation For tuberculosis case detection, sensitivity of Xpert Ultra was superior to that of Xpert in patients with paucibacillary disease and in patients with HIV. However, this increase in sensitivity came at the expense of a decrease in specificity. Funding Government of Netherlands, Government of Australia, Bill & Melinda Gates Foundation, Government of the UK, and the National Institute of Allergy and Infectious Diseases.

0 comments Cited 193 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): BMJ Open

Journal ID (iso-abbrev): BMJ Open

Journal ID (hwp): bmjopen

Journal ID (publisher-id): bmjopen

Title: BMJ Open

Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )

ISSN (Electronic): 2044-6055

Publication date Collection: 2022

Publication date (Electronic): 19 July 2022

Volume: 12

Issue: 7

Electronic Location Identifier: e060985

Affiliations

[1 ] Biomedical Research and Training Institute , Harare, Zimbabwe

[2 ] Instituto Nacional de Saúde , Marracuene, Mozambique

[3 ] National Institute for Medical Research- Mbeya Medical Research Centre , Mbeya, Tanzania

[4 ] Karolinska Institutet , Stockholm, Sweden

[5 ] departmentDepartment of Clinical Research, Faculty of Infectious and Tropical Diseases , London School of Hygiene & Tropical Medicine , London, UK

[6 ] departmentDivision of Infectious Diseases and Tropical Medicine , University Hospital, LMU Munich , Munich, Germany

[7 ] departmentGerman Center for Infection Research (DZIF) , Partner site Munich , Munich, Germany

Author notes

[Correspondence to ] Edson Tawanda Marambire; edsonmarambire@ 123456gmail.com

Author information

Edson Tawanda Marambire http://orcid.org/0000-0001-5944-5010

Article

Publisher ID: bmjopen-2022-060985

DOI: 10.1136/bmjopen-2022-060985

PMC ID: 9301805

SO-VID: 3d2a0814-9300-48ef-a69e-d7a6dc848787

License:

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

History

Date received : 11 January 2022

Date accepted : 23 June 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100010269, Wellcome Trust;

Award ID: 203905/Z/16/Z

Funded by: European Union;

Award ID: RIA2018D-2508-ERASE-TB

Funded by: German Center for Infection Research (DZIF);

Award ID: 02.710

Funded by: Cepheid, Inc.;

Award ID: N/A

Funded by: Swedish Research Council;

Award ID: 220-23602

Custom metadata

special-feature unlocked

ScienceOpen disciplines: Medicine

Keywords: tuberculosis,diagnostic microbiology,respiratory medicine (see thoracic medicine)

Data availability:

ScienceOpen disciplines: Medicine

Keywords: tuberculosis, diagnostic microbiology, respiratory medicine (see thoracic medicine)

Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study

Read this article at

Abstract

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Related collections

Point-Of-Care Testing for Tuberculosis

Most cited references 27

Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD Statement

Sensitivity, Specificity, and Predictive Values: Foundations, Pliabilities, and Pitfalls in Research and Practice

Xpert MTB/RIF Ultra for detection of Mycobacterium tuberculosis and rifampicin resistance: a prospective multicentre diagnostic accuracy study

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 36

Most referenced authors 1,218